Immunogenic Compositions

Abstract

The invention relates to a combination therapy that finds utility in the treatment or prophylaxis of infectious diseases, cancers, autoimmune diseases and related conditions. In particular, the combination therapy comprises the administration of a TH-1 cytokine, in particular IL-18, and an immunogenic composition, in particular a vaccine, comprising an antigen and a CpG adjuvant.

1 . A method of enhancing an immune response to an antigen in a mammal, comprising administering to the mammal a safe and effective amount of 1) an IL-18 polypeptide or bioactive fragment or variant thereof, and 2) an immunogenic composition comprising an antigen or immunogenic derivative thereof and a CpG adjuvant.  
   
   
       2 . The method according to  claim 2 , wherein the antigen or immunogenic derivative thereof is derived from an organism selected from the group of: Human Immunodeficiency virus HIV-1, human herpes simplex viruses, cytomegalovirus, Rotavirus, Epstein Barr virus, Varicella Zoster Virus, from a hepatitis virus such as hepatitis B virus, hepatitis A virus, hepatitis C virus and hepatitis E virus, from Respiratory Syncytial virus, parainfluenza virus, measles virus, mumps virus, human papilloma viruses, flaviviruses or Influenza virus, from  Neisseria  spp,  Moraxelia  spp,  Bordetella  spp;  Mycobacterium  spp., including  M. tuberculosis; Escherichia  spp, including enterotoxic  E. coli; Salmonella  spp,;  Listeria  spp;  Helicobacter  spp;  Staphylococcus  spp., including  S. aureus, S. epidermidis;; Borrelia  spp;  Chlamydia  spp., including  C. trachomatis, C. pneumoniae; Plasmodium  spp., including  P. falciparum; Toxoplasma  spp., and  Candida  spp.  
   
   
       3 . A method of reducing the severity of a cancer in a patient, comprising administering to a patient in need thereof a safe and effective amount of 1 ) an IL-18 polypeptide or bioactive fragment or variant thereof and 2) an immunogenic composition comprising a tumour-associated antigen or immunogenic derivative thereof and a CpG adjuvant.  
   
   
       4 . The method according to  claim 3 , wherein the tumour-associated antigen or immunogenic derivative thereof is selected from the group of: an antigen from the MAGE family, PRAME, BAGE, LAGE 1, LAGE 2, SAGE, HAGE, XAGE, PSA, PAP, PSCA, prostein, P501 S, HASH2, Cripto, B726, NY-BR1.1, P510, MUC-1, Prostase, STEAP, tyrosinase, telomerase, survivin, CASB616, P53, and her 2 neu.  
   
   
       5 . The method according to claims  1 , wherein the IL-18 polypeptide or bioactive fragment or variant thereof and the immunogenic composition are administered simultaneously, separately or sequentially in any order.  
   
   
       6 . The method according to  claim 5 , wherein the IL-18 polypeptide or bioactive fragment or variant thereof and the immunogenic composition are administered simultaneously in the form of a combined pharmaceutical preparation.  
   
   
       7 . The method according to claims  1 , wherein the IL-18 polypeptide or bioactive fragment or derivative thereof is from human or murine origin.  
   
   
       8 . The method according to  claim 7 , wherein IL-18 is the polypeptide of SEQ ID NO.6 or SEQ ID NO.7 or bioactive fragment or derivative thereof.  
   
   
       9 . The method according to claims  1 , wherein the CpG adjuvant comprises a Purine, Purine, C, G, pyrimidine, pyrimidine sequence.  
   
   
       10 . The method according to claims  1 , wherein said CpG adjuvant is selected from the group of: TCC ATG ACG TTC CTG ACG TT (SEQ ID NO:1); TCT CCC AGC GTG CGC CAT (SEQ ID NO:2); ACC GAT GAC GTC GCC GGT GAC GGC ACC ACG (SEQ ID NO:3); TCG TCG TTT TGT CGT TTT GTC GTT (SEQ ID NO:4); and TCC ATG ACG TTC CTG ATG CT (SEQ ID NO:5).  
   
   
       11 . The method according to claims  1 , wherein said CpG adjuvant contains at least two unmethylated CG repeats that are separated at least by 3 nucleotides.  
   
   
       12 . The method according to  claim 11 , wherein the immunostimulatory oligonucleotide contains at least two unmethylated CG repeats that are separated by 6 nucleotides.  
   
   
       13 . A combined preparation comprising as active ingredients the following individual components: (1) an IL-18 polypeptide or bioactive fragment or variant thereof and (2) immunogenic composition comprising an antigen and a CpG adjuvant, the active ingredients being for the simultaneous, separate or sequential use for the prophylaxis and/or treatment of infectious diseases, cancer, autoimmune diseases and related conditions.  
   
   
       14 . The combined preparation according to  claim 13 , wherein components (1) and (2) are admixed in a composition.  
   
   
       15 . The combined preparation according to  claim 13 , wherein the immunogenic composition comprises a tumour-associated antigen or immunogenic derivative thereof and is prophylactically or therapeutically active against cancer.  
   
   
       16 . The combined preparation according to  claim 15 , wherein the tumour-associated antigen or immunogenic derivative thereof is selected from the group of: an antigen from the MAGE family, PRAME, BAGE, LAGE 1, LAGE 2, SAGE, HAGE, XAGE, PSA, PAP, PSCA, prostein, P501S, HASH2, Cripto, B726, NY-BR1.1, P510, MUC-1, Prostase, STEAP, tyrosinase, telomerase, survivin, CASB616, P53, and her 2 neu.  
   
   
       17 . The combined preparation according to claims  13 , wherein the IL-18 polypeptide or bioactive fragment or derivative thereof is from human or murine origin.  
   
   
       18 . The combined preparation according to  claim 17 , wherein IL-18 is the polypeptide of SEQ ID NO.6 or SEQ ID NO.7 or an bioactive fragment or derivative thereof.  
   
   
       19 . The combined preparation according to claims  13 , wherein the CpG adjuvant comDrises a Purine, Purine, C, G, pyrimidine, pyrimidine sequence.  
   
   
       20 . The combined preparation as claimed in claims  13 , wherein the immunogenic composition additionally comprises an immunostimulant chemical selected from the group of: 3D-MPL, QS21, a mixture of QS21 and cholesterol, aluminium hydroxide, aluminium phosphate, tocopherol, and an oil in water emulsion.  
   
   
       21 . The combined preparation as claimed in  claim 20 , wherein the immunogenic composition adjuvant comprises 3D-MPL, CpG, QS21, cholesterol, an oil in water emulsion.  
   
   
       22 . The combined preparation as claimed in  claim 21 , wherein the oil in water emulsion comprises squalene, tocopherol and polyoxyethylenesorbitan monooleate (Tween 80).  
   
   
       23 . The combined preparation as claimed in  claim 20 , wherein the immunogenic composition comprises QS21, cholesterol and a CpG adjuvant.  
   
   
       24 . The combined preparation as claimed in claims  13 , wherein both active components are in the form of injectable solutions.  
   
   
       25 . A pharmaceutical kit comprising as active ingredients the following individual components: (1) an IL-18 polypeptide or bioactive fragment thereof and (2) an immunogenic composition comprising an antigen or immunogenic derivative thereof and a CpG adjuvant, the active ingredients being for the simultaneous, separate or sequential use for the prophylaxis and/or treatment of infectious diseases, cancer, and auto-immune diseases.  
   
   
       26 . The pharmaceutical kit according to  claim 25 , wherein the immunogenic composition comprises a tumour-associated antigen or immunogenic derivative thereof and is prophylactically or therapeutically active against cancer.  
   
   
       27 . The pharmaceutical kit according to  claim 26 , wherein the tumour-associated antigen or immunogenic derivative thereof is selected from the group of: an antigen from the MAGE family, PRAME, BAGE, LAGE 1, LAGE 2, SAGE, HAGE, XAGE, PSA, PAP, PSCA, prostein, P501S, HASH2, Cripto, B726, NY-BR1.1, P510, MUC-1, Prostase, STEAP, tyrosinase, telomerase, survivin, CASB616, P53, and her 2 neu.  
   
   
       28 . The combined preparation as claimed in claims  13  for use in medicine.  
   
   
       29 . The method as claimed in claims  1  that comprises the use of a combined preparation comprising as active ingredients the following individual comDonents: (1) an IL-18 Polypeptide or bioactive fragment or variant thereof and (2) immunogenic composition comprising an antigen and a CPG adjuvant, the active ingredients being for the simultaneous, separate or sequential use for the prophylaxis and/or treatment of infectious diseases, cancer, autoimmune diseases and related conditions.  
   
   
       30 .- 35 . (canceled)  
   
   
       36 . A method of treating a patient suffering from or susceptible to infectious diseases, cancer, autoimmune diseases and related conditions comprising administering an IL-18 polypeptide or bioactive fragment or derivative thereof to the patient, wherein the patient has already been primed with an immunogenic composition comprising an antigen or immunogenic derivative thereof and a CpG adjuvant.  
   
   
       37 . A method of treating a patient suffering from or susceptible to infectious diseases, cancer, autoimmune diseases and related conditions comprising administering an immunogenic composition comprising an antigen or immunogenic derivative thereof and a CpG adjuvant to the patient, wherein the patient has already been primed with an IL-18 polypeptide or bioactive fragment or derivative thereof.  
   
   
       38 . The method as claimed in  claim 36 , wherein the antigen is a tumour-associated antigen, and the cancer is selected from the group of: breast cancer, lung cancer, NSCLC, colon cancer, melanoma, ovarian cancer, bladder cancer, head and neck squanmous carcinoma, and esophageal cancer.  
   
   
       39 . The method according to  claim 36 , wherein the IL-18 polypeptide or bioactive fragment or derivative thereof is from human or murine origin.  
   
   
       40 . The method according to  claim 39 , wherein IL-18 is the polypeptide of SEQ ID NO:6 or SEQ ID NO:7 or bioactive fragment or derivative thereof.  
   
   
       41 . The method according to  claim 26 , wherein the CpG adjuvant comprises a Purine, Purine, C, G, pyrimidine, pyrimidine sequence.  
   
   
       42 . The combined preparation as claimed in  claim 13 , wherein the immunogenic composition additionally comprises at least two immunostimulant chemicals selected from the group of: 3D-MPL, QS21, a mixture of QS21 and cholesterol, aluminium hydroxide, aluminium phosphate, tocopherol, and an oil in water emulsion.